The objective of this study was to determine the effect of photocatalytic titanium dioxide nanoparticles on Pseudokirchneriena subcapitata. Endpoints for dose-response experiments included direct cell counts, lipid peroxidation, and chlorophyll a measurements. The average 4-day EC50 for Degussa P25 with 13 day old algae was 113 +/- 18 mg L-1. When the response was expressed in term of number of nano-TiO2 particle per algal cell, R-pc, the overall EC50 was 6.5 +/- 0.5 particles cell(-1) (log), or (3.3 +/- 0.0) x 10(6) particles cell(-1). Particle size was varied at a given mass concentration, and the results suggest a "critical" primary particle size, between 4 and 30 nm, at which the adverse effect of photocatalytic TiO2 nanoparticles was maximum. Scanning electron microscopy (SEM) images showed algal cells covered by non-uniform multiple layers of TiO2 nanoparticles. Surface coverage and membrane lipid peroxidation could be the major damage mechanisms to algae. This is further supported by the confocal images of algal cells by DNA staining. In summary, the adverse effects caused by TiO2 were influenced by both the primary and secondary particles size, which governed the physical/chemical properties of TiO2 and the interaction between TiO2 and algae. (C) 2011 Elsevier B.V. All rights reserved.